Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000145303 | SCV000192380 | uncertain significance | Seckel syndrome 1 | 2013-10-04 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000431332 | SCV000512213 | uncertain significance | not specified | 2015-08-20 | criteria provided, single submitter | clinical testing | A variant of unknown significance has been identified in the ATR gene. The S1142G variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The S1142G variant was not observed with any significant frequency in the 1000 Genomes Project and in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The S1142G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals; however Glycine has been seen at this position in evolution. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Illumina Laboratory Services, |
RCV000145303 | SCV001307573 | uncertain significance | Seckel syndrome 1 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Invitae | RCV001244890 | SCV001418141 | uncertain significance | not provided | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1142 of the ATR protein (p.Ser1142Gly). This variant is present in population databases (rs149008479, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with cancer (PMID: 15987455, 32522261). ClinVar contains an entry for this variant (Variation ID: 157977). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Genome- |
RCV000145303 | SCV003801668 | uncertain significance | Seckel syndrome 1 | 2023-02-08 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003126519 | SCV003801669 | uncertain significance | Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome | 2023-02-08 | criteria provided, single submitter | clinical testing |